The Different Effects of IFN-β and IFN-γ on the Tumor-Suppressive Activity of Human Amniotic Fluid-Derived Mesenchymal Stem Cells

Current studies have shown that type I or II interferon-modified mesenchymal stem cells have great potential for the application of tumor-targeted therapy, but the underlying mechanism remains largely elusive. Here, we compared the different effects of IFN-β and IFN-γ on the antitumor activity of human amniotic fluid-derived mesenchymal stem cells (AFMSCs) and revealed the potential mechanism. In detail, AFMSCs primed with IFN-β or IFN-β plus IFN-γ, not IFN-γ, inhibited the proliferation of cancer cells in an immunocompetent mouse H460 subcutaneous model, although they all inhibited the proliferation of cancer cells in an immunocompromised mouse H460 subcutaneous model. TRAIL expressed by IFN-β- or IFN-γ-primed AFMSCs specifically exerted the antitumor effect of AFMSCs. AFMSCs primed with IFN-γ highly expressed immunosuppressive molecule IDO1, but IFN-β counteracted the IFN-γ-initiated IDO1 expression. 1-MT (IDO1 inhibitor) decreased TRAIL, but increased IDO1 expression in AFMSCs primed with interferon. As a result, AFMSCs primed with IFN-β or IFN-γ had the antitumor activity, and 1-MT failed to enhance the antitumor effect of IFN-γ-primed AFMSC in vitro and in the immunocompromised mouse H460 subcutaneous model. Furthermore, the expression of TRAIL in AFMSCs was upregulated by apoptotic cancer cells and this positive feedback intensified the antitumor effects of IFNs-primed AFMSCs. The different target gene expression profiles of AFMSCs regulated by IFN-β and IFN-γ determined the different antitumor effects of IFN-β- and IFN-γ-primed AFMSCs on tumor cells. Our finding may help to explore a clinical strategy for cancer intervention by understanding the antitumor mechanisms of MSCs and interferon

Evaluation of Urban Thermal Comfort and Its Relationship with Land Use/Land Cover Change: A Case Study of Three Urban Agglomerations, China

With the acceleration of urbanization in China, the urban surface thermal environment has undergone significant changes. This work aims to calculate the urban thermal comfort index using a temperature and humidity model with the land surface temperature and relative humidity. It also aims to explain the association between the land use/land cover change (LUCC) and urban surface thermal environment of the Beijing–Tianjin–Hebei (BTH) Region, the Guangdong–Hong Kong-Macao Greater Bay Area (GBA) and the Yangtze River Delta (YZD) in 2020, 2015, 2010 and 2005 using geographically weighted regression. The results reveal that (1) the three urban agglomerations have substantial heat island intensity regions, which are clustered and zonally distributed, and the annual average rates of the heat island area growth in the three regions are 1.01%, 1.41% and 1.09%, respectively. (2) Many uncomfortable areas exist in the three urban agglomerations, with an exponential growth trend in summer, and the annual average proportion of the uncomfortable areas in the three regions are 60.8%, 56.8% and 49.4%, respectively. (3) From the spatial point of view, the high-thermal comfort index areas of Beijing, Tianjin, Hebei, Guangdong, Hong Kong and Macao expand to the coast, and the high-index areas of the Yangtze River Delta expand to the inland. In terms of time, the annual distribution of thermal comfort in Beijing–Tianjin–Hebei is discrete, but the annual distribution of thermal comfort in Guangdong, Hong Kong, Macao and the Yangtze River Delta is concentrated. (4) In LUCC, the change intensity in construction land has a remarkable effect on the change in thermal comfort. The areas where the thermal comfort index increases positively correlate with the areas where the construction land increases. This study enriches the research on the impact of LUCC on urban ecological performance, and thus provides the necessary scientific basis for urban environment construction

Downregulation of circ-ZNF609 Promotes Heart Repair by Modulating RNA N6-Methyladenosine-Modified Yap Expression

Circular RNAs take crucial roles in several pathophysiological processes. The regulatory role and its underlying mechanisms of circ-ZNF609 in the heart remains largely unknown. Here, we report that circ-ZNF609 is upregulated during myocardial ischemia/reperfusion (I/R) remodeling. Knockdown of circ-ZNF609 protects against acute I/R injury and attenuates left ventricle dysfunction after I/R remodeling in vivo. In vitro, circ-ZNF609 regulates cardiomyocyte survival and proliferation via modulating the crosstalk between Hippo-YAP and Akt signaling. Mechanically, N6-methyladenosine-modification is involved in the regulatory role of circ-ZNF609 on YAP. An in-depth study indicates that knockdown of circ-ZNF609 decreases the expression of YTHDF3 and further fine-tuned the accessibility of Yap mRNA to YTHDF1 and YTHDF2 to regulate YAP expression. circ-ZNF609 knockdown represents a promising therapeutic strategy to combat the pathological process of myocardial I/R injury

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions